The Arclight vs. traditional ophthalmoscope:a cross-over trial

BACKGROUND/OBJECTIVES: To compare skill acquisition of the new, cost-effective Arclight ophthalmoscope, with the traditional ophthalmoscope (TO), in medical students with no prior experience of ophthalmoscopy. SUBJECTS/METHODS: University of Dundee medical students took part in a cross-over trial. Students were divided into two groups and were alternately taught each device using a video tutorial. In period one, Group A was taught the TO first; Group B was taught the Arclight. They were then assessed using simulated objective, structured, clinical, examinations, examining four model heads with lettered fundal photographs of varying sizes of font. Groups crossed over following a 2-week washout period and were taught the second device and reassessed. A questionnaire was distributed to ascertain students’ opinions and preferences. RESULTS: Forty medical students participated. Overall, 92.5% of students performed better with the Arclight, irrespective of cross-over trial period. The mean difference in score in period one of the cross-over trial was 16.77 (95% CI: 11.63–21.93), with students performing better with the Arclight (p < 0.0001). The mean difference in score in period two was 8.02 (95% CI: 4.52–11.52), with students performing better with the Arclight (p < 0.0001). In addition, performance with the TO improved by 52.9% following initial exposure to the Arclight. The Arclight was the preferred device by 82.5% of students, and 82.5% of students would choose this device for future practice. CONCLUSION: Students performed better with and preferred the Arclight ophthalmoscope. The Arclight could be considered as a suitable alternative to the TO used for training medical students

Developing gene therapy for inherited retinal degenerations

The aim of this thesis was to evaluate the efficacy and safety of retinal gene therapy in a pre-clinical model of CDHR1-associated retinal degeneration – a hitherto untreatable, blinding disorder. Deep phenotyping of the Cdhr1-/- murine model demonstrated severe early deficits in cone and rod photoreceptor function followed by progressive photoreceptor cell death – recapitulating CDHR1 cone-rod dystrophy. Two AAV8 vectors expressing the full-length human CDHR1 coding sequence were designed, manufactured, validated and titrated in vivo. Sub-retinal injection of AAV8.GRK1.CDHR1.pA (1.5 x 108 vg) in Cdhr1-/- mice at 3-4 weeks of age resulted in functional rescue of cone and rod photoreceptors with improved response amplitudes and decreased implicit times to 12-months post-injection; a slowing of photoreceptor cell death with regeneration of full-length photoreceptor outer segments confirmed on ultrastructural analysis to 21-months post-injection; and a behavioural rescue effect on photopic and scotopic optomotor testing, sustained to 21-months post-injection. AAV8.GRK1.CDHR1.pA at 1.5 x 108 vg appeared safe in C57BL/6J mice by the same outcome measures to 22-months post-injection. Genetic prevalence estimates presented herein suggest more than 200,000 affected individuals worldwide. We characterised 146 individuals with biallelic variants in CDHR1, describing the retinal phenotype, natural history, genotype-phenotype associations, with 25 novel pathological sequence variants. This is the first therapy shown to improve retinal structure and function in a pre-clinical model of CDHR1-associated retinal degeneration. A patent to protect the vectors described herein has been filed on behalf of the University of Oxford, with commercial agreements obtained in preparation for an onward phase 1 clinical trial.</p